title: Evaluation of quality of life in PKU before and after introducing tetrahydrobiopterin (BH4); a prospective multi-center cohort study.
abstract: BACKGROUND
  Phenylketonuria (PKU) is a rare inborn error of metabolism caused by phenylalanine hydroxylase enzyme (PAH) deficiency. Treatment constitutes a strict Phe restricted diet with unpalatable amino acid supplements. Residual PAH activity enhancement with its cofactor tetrahydrobiopterin (BH4) is a novel treatment which increases dietary tolerance in some patients and permits dietary relaxation. Relaxation of diet may improve health related quality of life (HRQoL). This prospective cohort study aims to evaluate HRQoL of patients with PKU and effects of BH4 treatment on HRQoL.
  
  
  METHODS
  Patients aged 4years and older, diagnosed through newborn screening and early and continuously treated, were recruited from eight metabolic centers. Patients and mothers completed validated generic and chronic health-conditions HRQoL questionnaires (PedsQL, TAAQOL, and DISABKIDS) twice: before and after testing BH4 responsivity. Baseline results were compared to the general population. Data collected after BH4 testing was used to find differences in HRQoL between BH4 unresponsive patients and BH4 responsive patients after one year of treatment with BH4. Also a within patient comparison was performed to find differences in HRQoL before and after treatment with BH4.
  
  
  RESULTS
  69/81 (85%) patients completed the questionnaires before BH4 responsivity testing, and 45/69 (65%) participated again after testing. Overall PKU patients demonstrated normal HRQoL. However, some significant differences were found when compared to the general population. A significantly higher (thus better) score on the PedsQL was reported by children 8-12 years on physical functioning and by children 13-17 years on total and psychosocial functioning. Furthermore, adult patients reported significantly lower (thus worse) scores in the TAAQOL cognitive domain. 10 patients proved to be responsive to BH4 treatment; however improvement in their HRQoL after relaxation of diet could not be demonstrated.
authors.affiliation: Department of Pediatrics, Emma Children's Hospital, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Serwet
authors.initials: S
authors.lastname: Demirdas
authors.forename: Heleen
authors.initials: H
authors.lastname: Maurice-Stam
authors.forename: Carolien C A
authors.initials: CC
authors.lastname: Boelen
authors.forename: Floris C
authors.initials: FC
authors.lastname: Hofstede
authors.forename: Mirian C H
authors.initials: MC
authors.lastname: Janssen
authors.forename: Janneke G
authors.initials: JG
authors.lastname: Langendonk
authors.forename: Margot F
authors.initials: MF
authors.lastname: Mulder
authors.forename: M Estela
authors.initials: ME
authors.lastname: Rubio-Gozalbo
authors.forename: Francjan J
authors.initials: FJ
authors.lastname: van Spronsen
authors.forename: Maaike
authors.initials: M
authors.lastname: de Vries
authors.forename: Martha A
authors.initials: MA
authors.lastname: Grootenhuis
authors.forename: Annet M
authors.initials: AM
authors.lastname: Bosch
mesh_terms: D000293:Adolescent; D000328:Adult; D001708:Biopterins / Q000031:analogs & derivatives* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D015997:Neonatal Screening; D010661:Phenylketonurias / Q000188:drug therapy* / Q000523:psychology*; D011446:Prospective Studies; D011788:Quality of Life; D011795:Surveys and Questionnaires; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D001708:Biopterins; C003402:sapropterin
keywords: AMC; Academic Medical Center, Amsterdam; BH4; DISABKIDS; HRQoL; Health related quality of life; PAH; PKU; Pediatric Quality of Life Inventory Measurement Model ™; PedsQL; Phe; Phenylketonuria; QoL; Quality of life; SD; TAAQOL; TNO-AZL Adult Quality of Life; The DISABKIDS chronic generic module; health related quality of life; phenylalanine; phenylalanine hydroxylase; phenylketonuria; standard deviation; tetrahydrobiopterin (BH4)